In this study we developed and evaluated stable, biodegradable microspheres for controlled release of venlafaxine. For this purpose, polycaprolactone, a hydrophobic polymer was used in different ratios. Following are the drug to polymer ratios P1 (1:1), P2 (1:1.5), P3 (1:2), P4 (1:2.5) and P5 (1:3); employed to develop controlled release microspheres. Drug loading efficiency increased with increasing quantity of polycaprolactone. The mechanism of venlafaxine release was studied by applying First order, Zero order, Higuchi’s, Hixon-Crowell and korsmeyer-Peppas models to dissolution data. Higuchi model was found the best fit model followed by First order release. The mechanism of release was non-Fickian diffusion. All formulations showed an initial burst of 69.53%, 62.37%, 55.45%, 53.76% and 49.32% from P1, P2, P3, P4 and P5 formulations, respectively at the end of 1st h dissolution. P5 was the superior formulation in terms of reduced initial burst and after which sustained release occurred up to 8 hours. The developed microspheres were characterized by Fourier transform infra-red spectroscopy, scanning electron spectroscopy, differential scanning calorimetry and thermogravimetric analysis
